Portal vein thrombosis is a rare but well-known complication after abdominal surgery. To our knowledge, there have been no reports about this complication after cardiopulmonary bypass surgery. This can probably be explained by the variety of clinical pictures and difficulties in the establishment of a diagnosis of portal vein thrombosis. Among the possible trigger factors, bacteremia, that is usually caused by Bacteroides fragilis or by Escherichia coli, has been assessed. In this case, several blood culture specimens and fluid from abdominal paracentesis consistently grew coagulase-negative staphylococci which have been proved to be one of the most common pathogens in postoperative infection after cardiac surgery. The patient received clopidogrel before and after coronary artery bypass grafting. We speculate that in this clinical situation associated with coagulase-negative staphylococcal bacteremia, clopidogrel resistance may play an important role. The natural history of portal vein thrombosis in this case is complicated by massive fatal gastrointestinal bleeding from rupture of the esophageal varices. Emergency endoscopic therapy with esophageal variceal ligation, injection of a sclerosing solution and using of vasoconstrictive agents helped only in the first episode of bleeding. Portal vein thrombosis after coronary artery bypass grafting is a serious complication. The clinical picture of portal vein thrombosis may vary greatly and the presence of this condition should be suspected when faced with abdominal pain with gastrointestinal bleeding of unknown origin and sepsis.